tbuckley/cabot-search huggingface dataset:
Treatable traits: a comprehensive precision medicine approach in interstitial lung disease
Authors: Yet H. Khor, Vincent Cottin, Anne E. Holland, Yoshikazu Inoue, Vanessa M. McDonald, Justin Oldham, Elisabetta A. Renzoni, Anne Marie Russell, Mary E. Strek, Christopher J. Ryerson
Journal: European Respiratory Journal (2023)

Interstitial lung disease (ILD) is a diverse group of inflammatory and fibrotic lung conditions causing significant morbidity and mortality. A multitude of factors beyond the lungs influence symptoms, health-related quality of life, disease progression and survival in patients with ILD. Despite an increasing emphasis on multidisciplinary management in ILD, the absence of a framework for assessment and delivery of comprehensive patient care poses challenges in clinical practice. The treatable traits approach is a precision medicine care model that operates on the premise of individualised multidimensional assessment for distinct traits that can be targeted by specific interventions. The potential utility of this approach has been described in airway diseases, but has not been adequately considered in ILD. Given the similar disease heterogeneity and complexity between ILD and airway diseases, we explore the concept and potential application of the treatable traits approach in ILD. A framework of aetiological, pulmonary, extrapulmonary and behavioural and lifestyle treatable traits relevant to clinical care and outcomes for patients with ILD is proposed. We further describe key research directions to evaluate the application of the treatable traits approach towards advancing patient care and health outcomes in ILD.
One-stage hip revisions are as good as two-stage surgery to replace infected artificial hips
Authors: Helen Saul, Brendan Deeney, Samantha Cassidy, Jemma Kwint, Ashley Blom
Journal: BMJ (2023)

The study Blom AW, Lenguerrand, Strange S, et al. Clinical and cost effectiveness of single stage compared with two stage revision for hip prosthetic joint infection (INFORM): pragmatic, parallel group, open label, randomised controlled trial. BMJ 2022;379:e071281. To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/one-stage-hip-revisions-are-as-good-as-2-stage-surgery-to-replace-infected-artificial-hips/
Prevention of venous thromboembolism in patients with cancer
Authors: Saketh R Guntupalli, Daniel Spinosa, Stephanie Wethington, Ramez Eskander, Alok A Khorana
Journal: BMJ (2023)

Abstract Venous thromboembolism (VTE) is a major cause of both morbidity and mortality in patients with cancer. Venous thromboembolism, which includes both deep vein thrombosis and pulmonary embolism, affects a sizable portion of patients with malignancy and can have potentially life threatening complications. Accurate assessment of risk as well as diagnosis and treatment of this process is paramount to preventing death in this high risk population. Various risk models predictive of venous thromboembolism in patients with cancer have been developed, and knowledge of these rubrics is essential for the treating oncologist. Subgroups of particular interest are inpatients receiving chemotherapy, postoperative patients after surgical debulking, and patients undergoing radiotherapy. Numerous newer drugs have become available for the prevention of venous thromboembolism in patients with cancer who are at high risk of developing the disease. These include the class of drugs called direct oral anticoagulants, (DOACs) which do not require the same monitoring that other modalities have previously required and are taken by mouth, preventing the discomfort associated with subcutaneous strategies. The appropriate risk stratification and intervention to prevent venous thromboembolism are vital to the treatment of patients with cancer.
Airway T cells are a correlate of i.v. Bacille Calmette-Guerin-mediated protection against tuberculosis in rhesus macaques
Authors: Patricia A. Darrah, Joseph J. Zeppa, Chuangqi Wang, Edward B. Irvine, Allison N. Bucsan, Mark A. Rodgers, Supriya Pokkali, Joshua A. Hackney, Megha Kamath, Alexander G. White, H. Jacob Borish, L. James Frye, Jaime Tomko, Kara Kracinovsky, Philana Ling Lin, Edwin Klein, Charles A. Scanga, Galit Alter, Sarah M. Fortune, Douglas A. Lauffenburger, JoAnne L. Flynn, Robert A. Seder, Pauline Maiello, Mario Roederer
Journal: Cell Host & Microbe (2023)
HLA class I signal peptide polymorphism determines the level of CD94/NKG2–HLA-E-mediated regulation of effector cell responses
Authors: Zhansong Lin, Arman A. Bashirova, Mathias Viard, Lee Garner, Max Quastel, Maya Beiersdorfer, Wojciech K. Kasprzak, Marjan Akdag, Yuko Yuki, Pedro Ojeda, Sudipto Das, Thorkell Andresson, Vivek Naranbhai, Amir Horowitz, Andrew J. McMichael, Angelique Hoelzemer, Geraldine M. Gillespie, Wilfredo F. Garcia-Beltran, Mary Carrington
Journal: Nature Immunology (2023)
Unraveling the potential of 3D bioprinted immunomodulatory materials for regulating macrophage polarization: State-of-the-art in bone and associated tissue regeneration
Authors: Sayan Deb Dutta, Tejal V. Patil, Keya Ganguly, Aayushi Randhawa, Ki-Taek Lim
Journal: Bioactive Materials (2023)

Macrophage-assisted immunomodulation is an alternative strategy in tissue engineering, wherein the interplay between pro-inflammatory and anti-inflammatory macrophage cells and body cells determines the fate of healing or inflammation. Although several reports have demonstrated that tissue regeneration depends on spatial and temporal regulation of the biophysical or biochemical microenvironment of the biomaterial, the underlying molecular mechanism behind immunomodulation is still under consideration for developing immunomodulatory scaffolds. Currently, most fabricated immunomodulatory platforms reported in the literature show regenerative capabilities of a particular tissue, for example, endogenous tissue (e.g., bone, muscle, heart, kidney, and lungs) or exogenous tissue (e.g., skin and eye). In this review, we briefly introduced the necessity of the 3D immunomodulatory scaffolds and nanomaterials, focusing on material properties and their interaction with macrophages for general readers. This review also provides a comprehensive summary of macrophage origin and taxonomy, their diverse functions, and various signal transduction pathways during biomaterial-macrophage interaction, which is particularly helpful for material scientists and clinicians for developing next-generation immunomodulatory scaffolds. From a clinical standpoint, we briefly discussed the role of 3D biomaterial scaffolds and/or nanomaterial composites for macrophage-assisted tissue engineering with a special focus on bone and associated tissues. Finally, a summary with expert opinion is presented to address the challenges and future necessity of 3D bioprinted immunomodulatory materials for tissue engineering.
<scp>Large‐Scale</scp> Analysis of Meniscus Morphology as Risk Factor for Knee Osteoarthritis
Authors: Kenneth T. Gao, Emily Xie, Vincent Chen, Claudia Iriondo, Francesco Calivà, Richard B. Souza, Sharmila Majumdar, Valentina Pedoia
Journal: Arthritis & Rheumatology (2023)

Although it is established that structural damage of the meniscus is linked to knee osteoarthritis (OA) progression, the predisposition to future development of OA because of geometric meniscal shapes is plausible and unexplored. This study aims to identify common variations in meniscal shape and determine their relationships to tissue morphology, OA onset, and longitudinal changes in cartilage thickness.
Estimates of SARS-CoV-2 Seroprevalence and Incidence of Primary SARS-CoV-2 Infections Among Blood Donors, by COVID-19 Vaccination Status — United States, April 2021–September 2022
Authors: Jefferson M. Jones, Irene Molina Manrique, Mars S. Stone, Eduard Grebe, Paula Saa, Clara D. Germanio, Bryan R. Spencer, Edward Notari, Marjorie Bravo, Marion C. Lanteri, Valerie Green, Melissa Briggs-Hagen, Melissa M. Coughlin, Susan L. Stramer, Jean Opsomer, Michael P. Busch
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

Changes in testing behaviors and reporting requirements have hampered the ability to estimate the U.S. SARS-CoV-2 incidence (1). Hybrid immunity (immunity derived from both previous infection and vaccination) has been reported to provide better protection than that from infection or vaccination alone (2). To estimate the incidence of infection and the prevalence of infection- or vaccination-induced antibodies (or both), data from a nationwide, longitudinal cohort of blood donors were analyzed. During the second quarter of 2021 (April-June), an estimated 68.4% of persons aged ≥16 years had infection- or vaccination-induced SARS-CoV-2 antibodies, including 47.5% from vaccination alone, 12.0% from infection alone, and 8.9% from both. By the third quarter of 2022 (July-September), 96.4% had SARS-CoV-2 antibodies from previous infection or vaccination, including 22.6% from infection alone and 26.1% from vaccination alone; 47.7% had hybrid immunity. Prevalence of hybrid immunity was lowest among persons aged ≥65 years (36.9%), the group with the highest risk for severe disease if infected, and was highest among those aged 16-29 years (59.6%). Low prevalence of infection-induced and hybrid immunity among older adults reflects the success of public health infection prevention efforts while also highlighting the importance of older adults staying up to date with recommended COVID-19 vaccination, including at least 1 bivalent dose.*,†.
The association of alcohol dependence and consumption during adolescence with depression in young adulthood, in England: a prospective cohort study
Authors: Gemma Hammerton, Gemma Lewis, Jon Heron, Gwen Fernandes, Matthew Hickman, Glyn Lewis
Journal: The Lancet Psychiatry (2023)

The role of alcohol use in the development of depression is unclear. We aimed to investigate whether alcohol dependence, but not high frequency or quantity of consumption, during adolescence increased the risk of depression in young adulthood.
Methionine restriction promotes cGAS activation and chromatin untethering through demethylation to enhance antitumor immunity
Authors: Lan Fang, Yun Hao, Haihong Yu, Xuemei Gu, Qiao Peng, Huimin Zhuo, Yaxu Li, Zhiyuan Liu, Jia Wang, Yunfei Chen, Jiawen Zhang, Hongling Tian, Yaohui Gao, Renyuan Gao, Hongqi Teng, Zezhi Shan, Jiali Zhu, Zhiqiang Li, Yu’e Liu, Yiyi Zhang, Fei Yu, Zhang Lin, Yujun Hao, Xin Ge, Jian Yuan, Hong-Gang Hu, Yanlei Ma, Huan-Long Qin, Ping Wang
Journal: Cancer Cell (2023)

Cyclic GMP-AMP synthase (cGAS) is the major sensor for cytosolic DNA and activates type I interferon signaling and plays an essential role in antitumor immunity. However, it remains unclear whether the cGAS-mediated antitumor activity is affected by nutrient status. Here, our study reports that methionine deprivation enhances cGAS activity by blocking its methylation, which is catalyzed by methyltransferase SUV39H1. We further show that methylation enhances the chromatin sequestration of cGAS in a UHRF1-dependent manner. Blocking cGAS methylation enhances cGAS-mediated antitumor immunity and suppresses colorectal tumorigenesis. Clinically, cGAS methylation in human cancers correlates with poor prognosis. Thus, our results indicate that nutrient stress promotes cGAS activation via reversible methylation, and suggest a potential therapeutic strategy for targeting cGAS methylation in cancer treatment.
Discovery of novel aporphine alkaloid derivative as potent TLR2 antagonist reversing macrophage polarization and neutrophil infiltration against acute inflammation
Authors: Junjie Yang, Yue Pan, Xiaoshan Zeng, Shuwen Liu, Zhipeng Chen, Kui Cheng
Journal: Acta Pharmaceutica Sinica B (2023)

Toll-like receptor 2 (TLR2) mediated macrophages regulate the protective immune response to infectious microorganisms, but the aberrant activation of macrophages often leads to pathological inflammation, including tissue damage. In this study, we identified antagonists of TLR2 by screening 2100 natural products and subsequently identified Taspine, an aporphine alkaloid, as an excellent candidate. Furthermore, analysis of the 10 steps chemical synthesis route and structural optimization yielded the Taspine derivative SMU-Y6, which has higher activity, better solubility, and improved drug-feasible property. Mechanistic studies and seq-RNA analysis revealed that SMU-Y6 inhibited TLR2 over other TLRs, hindered the formation of TLR2/MyD88 complex, and blocked the downstream NF-κB and MAPK signaling pathway, thus suppressing the release of inflammatory cytokines. SMU-Y6 could stabilize TLR2 and bind to TLR2 protein with a Kd of 0.18 μmol/L. Additionally, SMU-Y6 could efficiently reverse the M1 phenotype macrophage polarization, reduce the production of cytokines as well as infiltration of neutrophiles and alleviate the local inflammation in mice with acute paw edema and colitis. Collectively, we reported the first aporphine alkaloid derivative that selectively inhibits TLR2 with high binding affinity and superior drug-feasible property, thus providing an urgently-needed molecular probe and potential drug candidate for inflammatory and autoimmune disease therapy.
A Non‐G‐Quadruplex DNA Aptamer Targeting NCL for Diagnosis and Therapy in Bladder Cancer
Authors: Yunyi Liu, Bei Hu, Xiaming Pei, Juan Li, Dan Qi, Yuxi Xu, Hailong Ou, Yatao Wu, Lei Xue, Jason H. Huang, Erxi Wu, Xiaoxiao Hu
Journal: Advanced Healthcare Materials (2023)

Bladder cancer (BC) is a highly aggressive malignant tumor affecting the urinary system, characterized by metastasis and a poor prognosis that often leads to limited therapeutic success. This study aims to develop a novel DNA aptamer for the diagnosis and treatment of BC using a tissue-based systematic evolution of ligands by an exponential enrichment (SELEX) process. By using SELEX, this work successfully generates a new aptamer named TB-5, which demonstrates a remarkable and specific affinity for nucleolin (NCL) in BC tissues and displays marked biocompatibility both in vitro and in vivo. Additionally, this work shows that NCL is a reliable tissue-specific biomarker in BC. Moreover, according to circular dichroism spectroscopy, TB-5 forms a non-G-quadruplex structure, distinguishing it from the current NCL-targeting aptamer AS1411, and exhibits a distinct binding region on NCL compared to AS1411. Notably, this study further reveals that TB-5 activates NCL function by promoting autophagy and suppressing the migration and invasion of BC cells, which occurs by disrupting mRNA transcription processes. These findings highlight the critical role of NCL in the pathological examination of BC and warrant more comprehensive investigations on anti-NCL aptamers in BC imaging and treatment.
Incidence and Characteristics of Hypersensitivity Reactions to PEG-asparaginase Observed in 6136 Children With Acute Lymphoblastic Leukemia Enrolled in the AIEOP-BFM ALL 2009 Study Protocol
Authors: Carmelo Rizzari, Anja Möricke, Maria Grazia Valsecchi, Valentino Conter, Martin Zimmermann, Daniela Silvestri, Andishe Attarbaschi, Felix Niggli, Draga Barbaric, Jan Stary, Sarah Elitzur, Gunnar Cario, Luciana Vinti, Joachim Boos, Massimo Zucchetti, Claudia Lanvers-Kaminsky, Arend von Stackelberg, Andrea Biondi, Martin Schrappe
Journal: HemaSphere (2023)

The incidence of hypersensitivity reactions (HSRs) to PEG-asparaginase (PEG-ASNase) was evaluated in 6136 children with ALL enrolled in the AIEOP-BFM ALL 2009 study. Patients with B-cell precursor-acute lymphoblastic leukemia (BCP-ALL) were stratified as standard-risk/medium-risk (MR)/high-risk (HR) and those with T-ALL as non-High/HR. PEG-ASNase was administered intravenously at 2500 IU/sqm/dose. All patients received 2 PEG-ASNase doses in induction; thereafter non-HR versus HR patients received 1 versus 6 PEG-ASNase doses, respectively. After the single regular dose of PEG-ASNase at the beginning of delayed intensification, BCP-ALL-MR patients were randomized to receive 9 additional PEG-ASNase doses every 2 weeks (experimental arm [EA]) versus none (standard arm [SA]); HR patients were randomized to receive, in consolidation, 4 weekly PEG-ASNase doses (EA) versus none (SA). The HSR cumulative incidence (CI) was estimated adjusting for competing risks. An HSR occurred in 472 of 6136 (7.7%) patients. T-non- HR/BCP-Standard-Risk, BCP-MR-SA, BCP-MR-EA, HR-SA and HR-EA patients had 1-year-CI-HSR (±SE) rates of 5.2% (0.5), 5.2% (0.5), 4.0% (0.8), 20.2% (1.2), and 6.4% (1.3), respectively. The randomized intensification of PEG-ASNase did not significantly impact on HSR incidence in BCP-MR patients (1-y-CI-HSR 3.8% [0.8] versus 3.2% [0.6] in MR-EA versus MR-SA; P = 0.55), while impacted significantly in HR patients (1-y-CI-HSR 6.4% [1.3] versus 17.9% [1.8] in HR-EA and HR-SA, respectively; P < 0.001). The CI-HSR was comparable among non-HR groups and was not increased by a substantial intensification of PEG-ASNase in the BCP-MR-EA group whilst it was markedly higher in HR-SA than in HR-EA patients, suggesting that, in such a chemotherapy context, a continuous exposure to PEG-ASNase reduces the risk of developing an HSR.
Uncertainty aware training to improve deep learning model calibration for classification of cardiac MR images
Authors: Tareen Dawood, Chen Chen, Baldeep S. Sidhu, Bram Ruijsink, Justin Gould, Bradley Porter, Mark K. Elliott, Vishal Mehta, Christopher A. Rinaldi, Esther Puyol-Antón, Reza Razavi, Andrew P. King
Journal: Medical Image Analysis (2023)

Quantifying uncertainty of predictions has been identified as one way to develop more trustworthy artificial intelligence (AI) models beyond conventional reporting of performance metrics. When considering their role in a clinical decision support setting, AI classification models should ideally avoid confident wrong predictions and maximise the confidence of correct predictions. Models that do this are said to be well calibrated with regard to confidence. However, relatively little attention has been paid to how to improve calibration when training these models, i.e. to make the training strategy uncertainty-aware. In this work we: (i) evaluate three novel uncertainty-aware training strategies with regard to a range of accuracy and calibration performance measures, comparing against two state-of-the-art approaches, (ii) quantify the data (aleatoric) and model (epistemic) uncertainty of all models and (iii) evaluate the impact of using a model calibration measure for model selection in uncertainty-aware training, in contrast to the normal accuracy-based measures. We perform our analysis using two different clinical applications: cardiac resynchronisation therapy (CRT) response prediction and coronary artery disease (CAD) diagnosis from cardiac magnetic resonance (CMR) images. The best-performing model in terms of both classification accuracy and the most common calibration measure, expected calibration error (ECE) was the Confidence Weight method, a novel approach that weights the loss of samples to explicitly penalise confident incorrect predictions. The method reduced the ECE by 17% for CRT response prediction and by 22% for CAD diagnosis when compared to a baseline classifier in which no uncertainty-aware strategy was included. In both applications, as well as reducing the ECE there was a slight increase in accuracy from 69% to 70% and 70% to 72% for CRT response prediction and CAD diagnosis respectively. However, our analysis showed a lack of consistency in terms of optimal models when using different calibration measures. This indicates the need for careful consideration of performance metrics when training and selecting models for complex high risk applications in healthcare.
Genome-wide association study of chronic sputum production implicates loci involved in mucus production and infection
Authors: Richard J. Packer, Nick Shrine, Robert Hall, Carl A. Melbourne, Rebecca Thompson, Alex T. Williams, Megan L. Paynton, Anna L. Guyatt, Richard J. Allen, Paul H. Lee, Catherine John, Archie Campbell, Caroline Hayward, Maaike de Vries, Judith M. Vonk, Jonathan Davitte, Edith Hessel, David Michalovich, Joanna C. Betts, Ian Sayers, Astrid Yeo, Ian P. Hall, Martin D. Tobin, Louise V. Wain
Journal: European Respiratory Journal (2023)

Chronic sputum production impacts on quality of life and is a feature of many respiratory diseases. Identification of the genetic variants associated with chronic sputum production in a disease agnostic sample could improve understanding of its causes and identify new molecular targets for treatment.
Erratum to “Identification of anti-Mycobacterium tuberculosis agents targeting the interaction of bacterial division proteins FtsZ and SepFe” [Acta Pharmaceutica Sinica B 13 (2023) 2056–2070]
Authors: Hongjuan Zhang, Ying Chen, Yu Zhang, Luyao Qiao, Xiangyin Chi, Yanxing Han, Yuan Lin, Shuyi Si, Jiandong Jiang
Journal: Acta Pharmaceutica Sinica B (2023)

[This corrects the article DOI: 10.1016/j.apsb.2023.01.022.].
<i>Notes from the Field:</i> Pediatric Intracranial Infections — Clark County, Nevada, January–December 2022
Authors: Jessica A. Penney, Ying Zhang, Taryn Bragg, Rachel Bryant, Cassius Lockett
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

In October 2022, the Southern Nevada Health District (SNHD) was notified of a higher-than-expected number of pediatric patients hospitalized with intracranial abscesses; similar concerns were previously reported nationally (1,2).This rare infection is associated with significant morbidity (3,4).When SNHD received the report in October 2022, 14 cases had been diagnosed in the largest pediatric hospital in southern Nevada.SNHD investigated the reported increase to confirm that a cluster had been detected, identify common risk factors for infection, report findings to the community, and recommend measures to prevent future cases.The observed and expected number of cases were compared to confirm and describe the cluster.Historical median quarterly case numbers with IQRs were obtained from discharge data from all hospitals in Clark County, Nevada during January 2015-December 2021.Persons with primary, secondary, or tertiary discharge diagnoses of intracranial abscess and granuloma (International Classification of Diseases, Tenth Revision, Clinical Modification [ICD-10-CM] code G06.0) or extradural and subdural abscess, unspecified (ICD-10-CM code G06.2) during January 2015-December 2022 among persons aged ≤18 years were identified as cases.Because hospital discharge data from the final quarter of 2022 were not available at the time of investigation, cases in 2022 were primarily identified through provider reporting and confirmed by discharge data, if available; for these data, a case was defined as diagnosis of an intraparenchymal abscess, subdural abscess or empyema, epidural abscess or empyema, or evidence of other intracranial extension observed on brain imaging in a person aged ≤18 years without a previous neurosurgical procedure or history of significant head trauma.Detailed medical chart abstraction and semistructured telephone interviews with families affected during 2022 were conducted to ascertain clinical course, risk factors, and exposures.This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy.*During 2015-2021 overall, a median of one case per quarter (IQR = 0-2.0)was identified in Clark County.However, during the period preceding the COVID-19 * 45 C.